Prevention of Anthracyclines and HER2 Inhibitor-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis.

BACKGROUND: This meta-analysis and systematic review aim to consolidate evidence on cardiotoxicity prevention and treatment strategies in patients receiving anthracyclines or HER2 receptor inhibitors, vital treatments for breast cancer and hematologic malignancies. By synthesizing existing research, the goal is to provide impactful insights that enhance patient care and outcomes. METHODS: Comprehensive research across PubMed, Scopus, EMBASE, and the Cochrane Central Register for Controlled Trials was conducted, selecting clinical trials focusing on cardioprotection in anthracyclines or HER2 inhibitor-treated individuals. Effect sizes were computed using OpenMeta (Analyst), with leave-out meta-analysis to assess potential small study effects. Meta-regression explored treatment duration and sample size effects. Evidence quality for primary outcomes was evaluated using ROB, Robins 2, and Newcastle-Ottawa tools. RESULTS: Twenty -three studies involving a total of 14,652 patients (13,221 adults and 1431 kids) were included in the current systematic review and meta-analysis. The risk of bias and methodological quality of the included studies suggested good and moderate quality. Patients prescribed ß-blockers demonstrated a 74% lower likelihood of exhibiting cardiotoxicity symptoms (OR 1.736). Similarly, the use of dexrazoxane was linked to a threefold decrease in cardiac abnormalities risk (OR 2.989), and ACE inhibitor administration showed half the risk compared with the control group (OR 1.956). CONCLUSIONS: Through this systematic review and meta-analysis, it was shown that there is a reduction in cardiotoxicity from either anthracyclines or HER2 inhibitors in patients receiving pharmacoprophylaxis.

Assessment of Myocardial Viability in Ischemic Cardiomyopathy With Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: We aim to provide a comprehensive review of the current state of knowledge of myocardial viability assessment in patients undergoing coronary artery bypass grafting (CABG), with a focus on the clinical markers of viability for each imaging modality. We also compare mortality between patients with viable myocardium and those without viability who undergo CABG. METHODS: A systematic database search with meta-analysis was conducted of comparative original articles (both observations and randomized controlled studies) of patients undergoing CABG with either viable or nonviable myocardium, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to 2022. Imaging modalities included were dobutamine stress echocardiography (DSE), cardiac magnetic resonance (CMR), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). RESULTS: A total of 17 studies incorporating a total of 2317 patients were included. Across all imaging modalities, the relative risk of death post-CABG was reduced in patients with versus without viability (random-effects model: odds ratio: 0.42; 95% confidence interval: 0.29-0.61; p < 0.001). Imaging for myocardial viability has significant clinical implications as it can affect the accuracy of the diagnosis, guide treatment decisions, and predict patient outcomes. Generally, based on local availability and expertise, either SPECT or DSE should be considered as the first step in evaluating viability, while PET or CMR would provide further evaluation of transmurality, perfusion metabolism, and extent of scar tissue. CONCLUSION: The assessment of myocardial viability is an essential component of preoperative evaluation in patients with ischemic heart disease undergoing surgical revascularization. Careful patient selection and individualized assessment of viability remain paramount.

Contemporary Use of Sodium Glucose Co-Transporter 2 Inhibitors in Hospitalized Heart Failure Patients: A "Real-World" Experience.

Background/Objectives: The aim of this study was to examine the association between in-hospital initiation of sodium glucose co-transporter 2 inhibitors (SGLT2is) and outcomes in hospitalized heart failure (HHF) patients utilizing data from a Greek center. Methods: The present work was a single-center, retrospective, observational study of consecutive HF patients hospitalized in a tertiary center. The study endpoint was all-cause mortality or HF rehospitalization. Univariate and multivariate Cox proportional-hazard models were conducted to investigate the association between SGLT2i administration at discharge and the study endpoint. Results: Sample consisted of 171 patients, 55 of whom (32.2%) received SGLT2is at discharge. Overall, mean follow-up period was 6.1 months (SD = 4.8 months). Patients who received SGLT2is at discharge had a 43% lower probability of the study endpoint compared to those who did not receive SGLT2is at discharge (HR = 0.57; 95% CI: 0.36-0.91; p = 0.018). After adjusting for age, gender, smoking, hemoglobin (Hgb), use of SGLT2is at admission, use of Angiotensin-Converting Enzyme Inhibitors (ACEI-Is)/Angiotensin Receptor Blockers (ARBs) at discharge and Sacubitril/Valsartan at discharge, the aforementioned result remained significant (HR = 0.38; 95% CI: 0.19-0.73; p = 0.004). The 55 patients who received SGLT2is at discharge were propensity score matched with the 116 patients who did not receive SGLT2is at discharge. Receiving SGLT2is at discharge continued to be significantly associated with a lower probability of the study endpoint (HR= 0.43; 95% CI: 0.20-0.89; p = 0.024). Conclusions: Initiation of SGLT2is in HHF patients may be associated with better outcomes.

Latest updates on structure and recommendations of cardiac rehabilitation programs in chronic heart failure.

Chronic heart failure (HF) is a clinical syndrome with high morbidity and mortality worldwide. Cardiac rehabilitation (CR) is a medically supervised program designed to maintain or improve cardiovascular health of people living with HF, recommended by both American and European guidelines. A CR program consists of a multispecialty group including physicians, nurses, physiotherapists, trainers, nutritionists, and psychologists with the common purpose of improving functional capacity and quality of life of chronic HF patients. Physical activity, lifestyle, and psychological support are core components of a successful CR program. CR has been shown to be beneficial in all ejection fraction categories in HF and most patients, who are stable under medication, are capable of participating. An individualized exercise prescription should be developed on the basis of a baseline evaluation in all patients. The main modalities of exercise training are aerobic exercise and muscle strength training of different intensity and frequency. It is important to set the appropriate clinical outcomes from the beginning, in order to assess the effectiveness of a CR program. There are still significant limitations that prevent patients from participating in these programs and need to be solved. A significant limitation is the generally low quality of research in CR and the presence of negative trials, such as the rehabilitation after myocardial infarction trial, where comprehensive rehabilitation following myocardial infraction had no important effect on mortality, morbidity, risk factors, or health-related quality of life or activity. In the present editorial, we present all the updated knowledge and recommendations in CR programs.

Valve Type and Operative Risks in Surgical Explantation of Transcatheter Aortic Valves: A Systematic Review and Meta-Analysis.

Indication to perform surgical explantation of TAVR is becoming increasingly more frequent, due to the higher number of transcatheter procedures performed in patients with longer life expectancy. We proposed to perform a systematic review and meta-analysis with metaregression to identify potential factors that can determine an increase in the high mortality and morbidity that characterize these surgical procedures. MEDLINE and Embase were searched for relevant studies. Twelve studies were eligible according to our inclusion criteria. TAVR explantation was confirmed as a procedure with high 30-day mortality (0.17; 95% CI, 0.14-0.21) and morbidity (stroke incidence 5%; 95% CI, 0.04-0.07; kidney injury incidence 16%; 95% CI, 0.11-0.24). The type of transcatheter valve implanted during the index procedure did not influence the outcomes after surgical explantation. The role of these high-risk operations is growing, and it will likely expand in the coming years. Specific tools for risk stratification are required.

Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

The Surgical Treatment of Infective Endocarditis: A Comprehensive Review.

Infective endocarditis (IE) is a severe cardiac complication with high mortality rates, especially when surgical intervention is delayed or absent. This review addresses the expanding role of surgery in managing IE, focusing on the variation in surgical treatment rates, the impact of patient demographics, and the effectiveness of different surgical approaches. Despite varying global data, a notable increase in surgical interventions for IE is evident, with over 50% of patients undergoing surgery in tertiary centres. This review synthesizes information from focused literature searches up to July 2023, covering preoperative to postoperative considerations and surgical strategies for IE. Key preoperative concerns include accurate diagnosis, appropriate antimicrobial treatment, and the timing of surgery, which is particularly crucial for patients with heart failure or at risk of embolism. Surgical approaches vary based on valve involvement, with mitral valve repair showing promising outcomes compared to replacement. Aortic valve surgery, traditionally favouring replacement, now includes repair as a viable option. Emerging techniques such as sutureless valves and aortic homografts are explored, highlighting their potential advantages in specific IE cases. The review also delves into high-risk groups like intravenous drug users and the elderly, emphasizing the need for tailored surgical strategies. With an increasing number of patients presenting with prosthetic valve endocarditis and device-related IE, the review underscores the importance of comprehensive management strategies encompassing surgical and medical interventions. Overall, this review provides a comprehensive overview of current evidence in the surgical management of IE, highlighting the necessity of a multidisciplinary approach and ongoing research to optimize patient outcomes.

Heart Transplantation.

Heart transplantation (HTx) remains the last therapeutic resort for patients with advanced heart failure. The present work is a clinically focused review discussing current issues in heart transplantation. Several factors have been associated with the outcome of HTx, such as ABO and HLA compatibility, graft size, ischemic time, age, infections, and the cause of death, as well as imaging and laboratory tests. In 2018, UNOS changed the organ allocation policy for HTx. The aim of this change was to prioritize patients with a more severe clinical condition resulting in a reduction in mortality of people on the waiting list. Advanced heart failure and resistant angina are among the main indications of HTx, whereas active infection, peripheral vascular disease, malignancies, and increased body mass index (BMI) are important contraindications. The main complications of HTx include graft rejection, graft angiopathy, primary graft failure, infection, neoplasms, and retransplantation. Recent advances in the field of HTx include the first two porcine-to-human xenotransplantations, the inclusion of hepatitis C donors, donation after circulatory death, novel monitoring for acute cellular rejection and antibody-mediated rejection, and advances in donor heart preservation and transportation. Lastly, novel immunosuppression therapies such as daratumumab, belatacept, IL 6 directed therapy, and IgG endopeptidase have shown promising results.

Artificial Intelligence in Heart Failure: Friend or Foe?

In recent times, there have been notable changes in cardiovascular medicine, propelled by the swift advancements in artificial intelligence (AI). The present work provides an overview of the current applications and challenges of AI in the field of heart failure. It emphasizes the "garbage in, garbage out" issue, where AI systems can produce inaccurate results with skewed data. The discussion covers issues in heart failure diagnostic algorithms, particularly discrepancies between existing models. Concerns about the reliance on the left ventricular ejection fraction (LVEF) for classification and treatment are highlighted, showcasing differences in current scientific perceptions. This review also delves into challenges in implementing AI, including variable considerations and biases in training data. It underscores the limitations of current AI models in real-world scenarios and the difficulty in interpreting their predictions, contributing to limited physician trust in AI-based models. The overarching suggestion is that AI can be a valuable tool in clinicians' hands for treating heart failure patients, as far as existing medical inaccuracies have been addressed before integrating AI into these frameworks.

The sympathetic nervous system in heart failure revisited.

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity.

Transcriptomic Analysis of Tight Junction Proteins Demonstrates the Aberrant Expression and Function of Zona Occludens 2 (ZO-2) Protein in Stanford Type A Aortic Dissection.

OBJECTIVE: Thoracic aortic aneurysm dissection (TAAD) represents a cardiac surgery emergency characterized by the disrupted integrity of the aortic wall and is associated with poor prognosis. In this context, the identification of biomarkers implicated in the pathobiology of TAAD is crucial. Our aim in the present original in silico study is to assess the differential gene expression profile of the tight junction proteins (TJPs) in patients with TAAD and to propose novel biomarkers for the diagnosis and prognosis of this disease. METHODS: We implemented bioinformatics methodology in order to construct the gene network of the TJPs family, identify the differentially expressed genes (DEGs) in pathologic aortic tissue excised from patients with TAAD as compared to healthy aortic tissue, and assess the related biological functions and the associated miRNA families. RESULTS: Data regarding the transcriptomic profile of selected genes were retrieved and incorporated from three microarray datasets, including 23 TAAD and 20 healthy control samples. A total of 32 TJPs were assessed. The zona occludens 2 (ZO-2) protein encoded by the gene TJP2 was significantly under-expressed in patients with TAAD compared to the control group (p = 0.009). ZO-2 was associated with fair discrimination and calibration traits in predicting the TAAD presentation. CpG islands of ZO-2 were demonstrated. No important difference was found regarding ZO-2 expression between aneurysmal non-dissected and healthy control aortic tissue. Finally, we performed gene set enrichment analysis (GSEA) and uncovered the major biological functions and miRNA families (hsa-miR-155-5p, hsa-miR-1-3p, hsa-miR-2118-5p, hsa-miR-4691-3p, and hsa-miR-1229-3p) relevant to ZO-2. CONCLUSIONS: These outcomes demonstrated the important role of ZO-2 in the pathobiology of TAAD.

Analysis of the Larissa Heart Failure Risk Score: Predictive Value in 9207 Patients Hospitalized for Heart Failure from a Single Center.

Early risk stratification is of outmost clinical importance in hospitalized patients with heart failure (HHF). We examined the predictive value of the Larissa Heart Failure Risk Score (LHFRS) in a large population of HHF patients from the Cleveland Clinic. A total of 13,309 admissions for heart failure (HF) from 9207 unique patients were extracted from the Cleveland Clinic's electronic health record system. For each admission, components of the 3-variable simple LHFRS were obtained, including hypertension history, myocardial infarction history, and red blood cell distribution width (RDW) ≥ 15%. The primary outcome was a HF readmission and/or all-cause mortality at one year, and the secondary outcome was all-cause mortality at one year of discharge. For both outcomes, all variables were statistically significant, and the Kaplan-Meier curves were well-separated and in a consistent order (Log-rank test p-value < 0.001). Higher LHFRS values were found to be strongly related to patients experiencing an event, showing a clear association of LHFRS with this study outcomes. The bootstrapped-validated area under the curve (AUC) for the logistic regression model for each outcome revealed a C-index of 0.64 both for the primary and secondary outcomes, respectively. LHFRS is a simple risk model and can be utilized as a basis for risk stratification in patients hospitalized for HF.

Sizing the Frozen Elephant Trunk Based on Aortic Pathology and the Importance of Pre-Operative Imaging.

The frozen elephant trunk is a formidable tool for the aortovascular surgeon. An appreciation of how to size the graft in different pathologies is key in achieving optimal results. Herein, we demonstrate worked examples of how imaging can be used to plan for a frozen elephant trunk and discuss the nuisances and uncertainties of sizing using three index cases: Type A aortic dissection, distal thoracic aortic aneurysm and chronic dissection.

Pneumomediastinum: Experience with 87 Patients.

OBJECTIVE: The aim of the present series was first to present our experience in the management of 37 patients with spontaneous pneumomediastinum (SPM), and further to indicate the necessity of identifying true SPM cases as they are currently inadequately defined. METHODS: This is a single-center, retrospective study, conducted in a university hospital. Consecutive adult patients with pneumomediastinum (PM) between January 2009 and March 2020 were involved in the series. The data about age, gender, symptoms, signs, treatment, length of hospital stay (LOS), and in-hospital mortality were evaluated. RESULTS: In total, 87 cases with pneumomediastinum (37 with spontaneous and 50 with secondary PM) were analyzed. Patients in both groups were of similar ages (P=0.4). Sufferers with secondary PM were more likely to have: an associated pneumothorax (19% vs 58%, P<0.05), a chest tube placed (18.9% vs 58%, P<0.05), an associated pleural effusion (0% vs 18%, P<0.05). They presented with a longer LOS (3.9 vs 5.3 days, P<0.05), and were more likely to die (0% vs 10%, P<0.05). Additionally they showed a higher prevalence of radiologic subcutaneous emphysema (49% vs 74%, P<0.05). CONCLUSION: Spontaneous pneumomediastinum is an onset of clinical importance with a low mortality rate, short LOS and good longterm prognosis. It often presents with chest pain, dyspnea and/or subcutaneous emphysema. However, secondary causes of mediastinal air must be ruled out, due to their potential devastating outcome if not diagnosed promptly. A consensus aimed at an update of the classification guidelines is more than indispensable.

The Sympathetic Nervous System in Hypertensive Heart Failure with Preserved LVEF.

The neurohormonal model of heart failure (HF) pathogenesis states that a reduction in cardiac output caused by cardiac injury results in sympathetic nervous system (SNS) activation, that is adaptive in the short-term and maladaptive in the long-term. This model has proved extremely valid and has been applied in HF with a reduced left ventricular (LV) ejection fraction (LVEF). In contrast, it has been undermined in HF with preserved LVEF (HFpEF), which is due to hypertension (HTN) in the vast majority of the cases. Erroneously, HTN, which is the leading cause of cardiovascular disease and premature death worldwide and is present in more than 90% of HF patients, is tightly linked with SNS overactivity. In this paper we provide a contemporary overview of the contribution of SNS overactivity to the development and progression of hypertensive HF (HHF) as well as the clinical implications resulting from therapeutic interventions modifying SNS activity. Throughout the manuscript the terms HHF with preserved LVEF and HfpEF will be used interchangeably, considering that the findings in most HFpEF studies are driven by HTN.

Efficacy of Granulocyte Colony-Stimulating Factor in Acute on Chronic Liver Failure: A Systematic Review and Survival Meta-Analysis.

BACKGROUND: Acute-on-chronic liver failure (ACLF) mostly occurs when there is an acute insult to the liver in patients with pre-existing liver disease, and it is characterized by a high mortality rate. Various therapeutic approaches have been used thus far, with orthotopic liver transplantation being the only definitive cure. Clinical trials and meta-analyses have investigated the use of granulocyte colony-stimulating factor (G-CSF) to mobilize bone marrow-derived stem cells. Some studies have suggested that G-CSF may have a significant role in the management and survival of patients with ACLF. However, the results are conflicting, and the efficacy of G-CSF still needs to be confirmed. AIM: The aim was to assess the efficacy of G-CSF in patients with ACLF. METHODS: Electronic databases were searched until May 2023 for randomized controlled trials investigating the use of G-CSF in adult patients with ACLF. Outcome measures were the effects of G-CSF on overall survival, changes in liver disease severity scores, complications of cirrhosis, other G-CSF-related adverse effects, and all-cause mortality. The study's protocol has been registered with Prospero (CRD42023420273). RESULTS: Five double-blind randomized controlled trials involving a total of 421 participants met the inclusion criteria. The use of G-CSF demonstrated a significant effect on overall survival (HR 0.63, 95% CI 0.41 to 0.95, and I2 48%), leading to a decreased mortality (LogOR-0.97, 95% CI -1.57 to -0.37, and I2 37.6%) and improved Model for End-Stage Liver Disease (MELD) scores (SMD -0.87, 95% CI -1.62 to -0.13, and I2 87.3%). There was no correlation between the improvement of the Child-Pugh score and the use of G-CSF(SMD -2.47, 95% CI -5.78 to 0.83, and I2 98.1%). The incidence of complications of cirrhosis did not decrease significantly with G-CSF treatment (rate ratio 0.51, 95% CI 0.26 to 1.01, and I2 90%). A qualitative synthesis showed that the use of G-CSF is safe. CONCLUSIONS: The administration of G-CSF has demonstrated a positive impact on overall survival, liver function, and the MELD score. The presence of heterogeneity in the included studies prohibits conclusive recommendations.